Exploring the Single-Cell Dynamics of FOXM1 Under Cell Cycle Perturbations.

IF 5.9 1区 生物学 Q2 CELL BIOLOGY
Tooba Jawwad, Maliwan Kamkaew, Kriengkrai Phongkitkarun, Porncheera Chusorn, Supawan Jamnongsong, Eric W-F Lam, Somponnat Sampattavanich
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Abstract

The cell cycle is crucial for maintaining normal cellular functions and preventing replication errors. FOXM1, a key transcription factor, plays a pivotal role in regulating cell cycle progression and is implicated in various physiological and pathological processes, including cancers like liver, prostate, breast, lung and colon cancer. Despite previous research, our understanding of FOXM1 dynamics under different cell cycle perturbations and its connection to heterogeneous cell fate decisions remains limited. In this study, we investigated FOXM1 behaviour in individual cells exposed to various perturbagens. We found that different drugs induce diverse responses due to heterogeneous FOXM1 dynamics at the single-cell level. Single-cell analysis identified six distinct cellular phenotypes: on-time cytokinesis, cytokinesis delay, cell cycle delay, G1 arrest, G2 arrest and cell death, observed across different drug types and doses. Specifically, treatments with PLK1, CDK1, CDK1/2 and Aurora kinase inhibitors revealed varied FOXM1 dynamics leading to heterogeneous cellular outcomes. Our findings affirm that the dynamics of FOXM1 are essential in shaping cellular outcomes, influencing the signals that dictate responses to various stimuli. Our results gave insights into how FOXM1 dynamics contribute to cell cycle fate decisions, especially under different cell cycle perturbations.

探索细胞周期扰动下FOXM1的单细胞动力学。
细胞周期对于维持正常细胞功能和防止复制错误至关重要。FOXM1是一种关键的转录因子,在调节细胞周期进程中起着关键作用,并涉及各种生理和病理过程,包括肝癌、前列腺癌、乳腺癌、肺癌和结肠癌等癌症。尽管之前有研究,但我们对不同细胞周期扰动下FOXM1动力学及其与异质细胞命运决定的联系的理解仍然有限。在这项研究中,我们研究了暴露于各种摄动原的单个细胞中的FOXM1行为。我们发现,由于FOXM1在单细胞水平上的异质性动力学,不同的药物诱导不同的反应。单细胞分析确定了六种不同的细胞表型:按时胞质分裂、胞质分裂延迟、细胞周期延迟、G1停滞、G2停滞和细胞死亡,这些表型在不同的药物类型和剂量下观察到。具体来说,使用PLK1、CDK1、CDK1/2和Aurora激酶抑制剂治疗显示FOXM1动力学变化导致细胞结果异质性。我们的研究结果证实FOXM1的动态在形成细胞结果、影响指示对各种刺激反应的信号方面是必不可少的。我们的研究结果揭示了FOXM1动力学如何影响细胞周期命运的决定,特别是在不同的细胞周期扰动下。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Proliferation
Cell Proliferation 生物-细胞生物学
CiteScore
14.80
自引率
2.40%
发文量
198
审稿时长
1 months
期刊介绍: Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.
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